Final Diagnosis -- Medulloblastoma, WHO Grade IV, consistent with late drop metastasis

DIAGNOSIS

Medulloblastoma, WHO Grade IV, consistent with late drop metastasis.

DISCUSSION

Medulloblastoma, an embryonal tumor of the posterior fossa, is the most common CNS malignant tumor of childhood, accounting for approximately 25% of all brain tumors in the pediatric population (6). Although a bimodal age distribution is well described with one peak in childhood and the second peak in the 3rd and 4th decades of life, medulloblastoma is a relatively rare tumor in adults, representing approximately 1% of all adult CNS tumors(8).

Overall, prognosis and treatment are similar for pediatric and adult medulloblastoma(1), with surgery and craniospinal radiation being the mainstay of treatment. Recurrences are common in both populations, and therefore, close follow-up is recommended. In children, most recurrences occur within the first 2 years following initial diagnosis. Pediatric medulloblastomas may follow Collins' law, which is defined as recurrence occurring within 9 months plus the age at initial diagnosis (3), albeit multiple cases have been reported to violate Collins' law (2). In adults, recurrence of medulloblastoma is common (1) and usually occurs after 2 years following initial diagnosis. Very late recurrences of adult medulloblastoma occurring greater than 20 years after initial diagnosis is extremely rare and only two previous cases have been reported in the literature thus far.

The first report by Cieslak et. al. described a 47-year-old woman who was initially diagnosed with medulloblastoma of the right cerebellar hemisphere at the age of 24(4). She underwent preoperative shunt and subtotal resection followed by craniospinal irradiation, 3600 R to the posterior fossa and 3000 R to the spinal cord. Twenty-three years later, the patient presented with a 3 month history of ataxia and right facial numbness. An MRI showed a right cerebellar tumor and pathologic diagnosis revealed recurrence of medulloblastoma at the site of the primary tumor.

Jouanneau et. al. reported the second case of very late recurrence of adult medulloblastoma(9). The patient was a 45-year-old man who was initially diagnosed with medulloblastoma located in the left cerebellar hemisphere at the age of 24 years old. Treatment for the primary tumor involved preoperative shunt, and complete resection followed by chemotherapy and craniospinal radiotherapy, 30 Gy with a 50 Gy boost to the posterior fossa. Twenty-one years later, the patient presented with diplopia and an MRI revealed a midline frontal lobe tumor that was close to the anterior cranial base. Pathologic diagnosis was metastatic medulloblastoma occurring in the frontal lobe 21 years after initial diagnosis.

We report the 3rd case of very late recurrence of adult medulloblastoma and the 2nd case report of very late recurrence occurring outside of the posterior fossa in an adult. Neuroimaging studies revealed an intradural extramedullary tumor with the main differential diagnosis of recurrent medulloblastoma versus ependymoma, astrocytoma, hemangioblastoma, metastatic disease, lymphoma or radiation necrosis. Given the patient's history, the diagnosis of recurrent medulloblastoma, late drop metastasis was favored. Intraoperatively, the tumor appeared primarily leptomeningeal with some involvement of the spinal roots. Although tumor histology and synaptophysin staining were consistent with medulloblastoma, this was a highly unusual diagnosis given the fact that the patient's initial diagnosis was made 22 years prior and he had no other sites of disease recurrence. The prominent expression of GFAP on scattered neoplastic cells was noteworthy. However, GFAP staining in medulloblastoma has been described in the literature and has shown a particular predilection for the nodular/desmoplastic variant of medulloblastoma(10), a variant that is more frequently seen in the adult population (1). The tumor that we describe displayed a vague nodular pattern, possibly explaining the observed GFAP expression.

Factors predisposing to late recurrences of medulloblastoma can only be based on speculation given the limited number of cases reported in the current literature. Although it is common for adult medulloblastoma to recur, late recurrences are rare and may be attributable to a break down in tumor immunosurveillance as a consequence of normal aging of the immune system with subsequent increase in tumor burden.

Leptomeningeal spread is characteristic of medulloblastoma(5), and drop metastasis to the spinal cord is the most common location. Current in vitro studies implicate a role for alpha-1 integrin expressed by medulloblastoma cells that mediates adhesion to extracellular matrix proteins of the leptomeninges with subsequent activation and proliferation of tumor cells(7). Application of these in vitro models to intra-axial metastatic medulloblastoma may provide further insight into the pathogenic mechanism of leptomeningeal spread and, in turn, may hold promise for the development of future strategies to prevent late recurrences of medulloblastoma.

Although late recurrence of adult medulloblastoma occurring more than 20 years after initial diagnosis is uncommon, consideration of this diagnosis is warranted when working up a CNS lesion in a patient with a remote history of treated medulloblastoma.

REFERENCES

1. Abacioglu U, Uzel O, Sengoz M, Turkan S, Ober A (2002) Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys.54(3):855-60.
2. Amagasaki K, Yamazaki H, Koizumi H, Hashizume K, Sasaguchi N (1999) Recurrence of medulloblastoma 19 years after the initial diagnosis. Childs Nerv Syst.15(9):482-5.
3. Brown WD, Tavare CJ, Sobel EL, Gilles FH (1995) Medulloblastoma and Collins' law: a critical review of the concept of a period of risk for tumor recurrence and patient survival. Neurosurgery.36(4):691-7.
4. Cieslak E, Kepka L, Fijuth J, Marchel A, Kroh H (2004) Very late relapse of medulloblastoma. Folia Neuropathol.42(1):49-53.
5. David KM, Casey AT, Hayward RD, Harkness WF, Phipps K, Wade AM (1997) Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from a single institution. J Neurosurg.86(1):13-21.
6. Farwell JR, Dohrmann GJ, Flannery JT (1977) Central nervous system tumors in children. Cancer.40(6):3123-32.
7. Fiorilli P, Partridge D, Staniszewska I, Wang JY, Grabacka M, So K, Marcinkiewicz C, Reiss K, Khalili K, Croul SE (2008) Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation. Lab Invest.88(11):1143-56.
8. Giordana MT, Schiffer P, Lanotte M, Girardi P, Chio A (1999) Epidemiology of adult medulloblastoma. Int J Cancer.80(5):689-92.
9. Jouanneau E, Guzman Tovar RA, Desuzinges C, Frappaz D, Louis-Tisserand G, Sunyach MP, Jouvet A, Sindou M (2006) Very late frontal relapse of medulloblastoma mimicking a meningioma in an adult: usefulness of 1H magnetic resonance spectroscopy and diffusion-perfusion magnetic resonance imaging for preoperative diagnosis: case report. Neurosurgery.58(4):E789; discussion E.
10. Weeks DA, Malott RL, Goin L, Mierau GW (2003) Ultrastructural spectrum of medulloblastoma with immunocytochemical correlations. Ultrastruct Pathol.27(2):101-7.

Contributed by Mary Ann Sanders, M.D.,Ph.D., Todd Vitaz, M.D., Marc Rosenblum, M.D., Alexis R. Plaga, Joseph C. Parker, Jr., M.D., and John R. Parker, M.D.